Basic research on anti-tumor effects of Interferon-α on hepatocellular carcinoma

干扰素-α抗肝癌作用的基础研究

基本信息

  • 批准号:
    13670233
  • 负责人:
  • 金额:
    $ 1.92万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2003
  • 项目状态:
    已结题

项目摘要

[Purpose] In this study, we examined that the effects of IFN-α subtypes on the growth of human liver cancer cell lines in vitro ; growth inhibitory effects of IFN-α and 5-Fu in vitro ; mechanisms of apoptosis induction by IFN-α; and the effects of IFN-α alone or IFN-α plus 5-Fu on the growth of human liver cancer cell lines transplanted In nude mice.[Results] 1. When we examined the effects of five kinds of recombinant IFN-α subtypes (α1, α2, α5, α8, α10; concentrations: 0-1024 IU/mL; 24-96 hours) on the growth of 13 human liver cancer cell lines, the strongest anti-proliferative effects was noted In IFN-α5 subtype, and followed by α8, α10, α2, α1. 2. No synergistic growth Inhibitory effects could be recognized when IFN-α and 5-Fu were simultaneously added t o the culture of liver cancer cells. 3. Natural human IFN-α induced activation of caspase-3, -7, -8, and -9, and proteolysis of PARP in IFN-α-induced apoptosis-sensitive cell lines at various degrees. In addition, release of cytochrome C and Smac/Diablo from mitochondria into cytoplasm was identified in IFN-α-treated cells time-dependently. These findings suggest mitochondria apoptosis induction pathway is involved in the IFN-α-induced apoptosis. 4. Subcutaneous IFN-αCon1 injection (0.01, 0.1, 1μg/mouse/day; 0.01 μg/mouse = clinical dosesage) for consecutive 14 days dose-and time-dependently suppressed the HCC tumor growth in nude mice. Finally, the tumor volumes of mice received 0.01, 0.1, and 1 μg/mouse of IFN-αCon1 decreased to about 60%, 25%,and 0-10%, respectively, of control tumor volumes. The number of apoptotic cells significantly Increased and the number of blood vessels significantly decreased with the increase of IFN-αCon1 dose. 5. Synergistic effect of IFN-α plus 5-Fu was identified In nude mouse tumors. [Conclusions] These data Indicate the potential clinical application of certain types of IFN-α in the prevention and treatment of HCC.
【目的】本研究探讨IFN-α亚型对人肝癌细胞系体外生长的影响;IFN-α和5-Fu的体外生长抑制作用;IFN-α诱导细胞凋亡的机制;以及IFN-α单独或IFN-α + 5-Fu对裸鼠移植人肝癌细胞株生长的影响。[结果]1。我们检测了5种重组IFN-α亚型(α1、α2、α5、α8、α10,浓度0 ~ 1024 IU/mL, 24 ~ 96 h)对13株人肝癌细胞株生长的影响,其中IFN-α5亚型的抗增殖作用最强,其次是α8、α10、α2、α1。2. 当IFN-α和5-Fu同时加入肝癌细胞培养时,未发现协同生长抑制作用。3. 在IFN-α诱导的凋亡敏感细胞系中,天然人IFN-α不同程度地诱导caspase-3、-7、-8和-9的激活以及PARP的蛋白水解。此外,在IFN-α-处理的细胞中,细胞色素C和Smac/Diablo从线粒体释放到细胞质中具有时间依赖性。提示线粒体凋亡诱导途径参与了IFN-α-诱导的细胞凋亡。4. 皮下注射IFN-αCon1(0.01、0.1、1μg/小鼠/天,0.01 μg/小鼠为临床剂量)连续14 d抑制裸鼠肝癌肿瘤生长。结果表明,注射0.01、0.1和1 μg/只IFN-αCon1后,小鼠肿瘤体积分别减少至对照肿瘤体积的60%、25%和0-10%左右。随着IFN-αCon1剂量的增加,凋亡细胞数量显著增加,血管数量显著减少。5. 在裸鼠肿瘤中发现IFN-α + 5-Fu的协同作用。[结论]这些数据提示某些类型的IFN-α在预防和治疗HCC中的潜在临床应用。

项目成果

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YANO Hirohisa其他文献

YANO Hirohisa的其他文献

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{{ truncateString('YANO Hirohisa', 18)}}的其他基金

Identification of diagnostic marker of combined hepatocellular-cholangiocarcinoma subtypes by gene expression analysis
通过基因表达分析鉴定肝细胞胆管癌联合亚型的诊断标志物
  • 批准号:
    18K07032
  • 财政年份:
    2018
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Basic studies on the treatment and prevention of hepatocellular carcinoma with interferon
干扰素治疗和预防肝细胞癌的基础研究
  • 批准号:
    19590412
  • 财政年份:
    2007
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
SUTUDIES ON THE RELATIONSHIP BETWEEN EPIDERMAL GROWTH FACTOR FAMILY EXPRESSION AND CARCINIGENESIS AND PROGESSION OF HEPATODELLULAR CRACINOMA : A SPECIAL REFERENCE TO HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR EXPRESSION
表皮生长因子家族表达与肝细胞癌癌变和进展关系的研究:肝素结合表皮生长因子样生长因子表达的特殊参考
  • 批准号:
    09670242
  • 财政年份:
    1997
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Towards Eradication: Reducing Proviral HIV DNA with Interferon-α Immunotherapy
走向根除:用干扰素-α 免疫疗法减少 HIV 病毒 DNA 前体
  • 批准号:
    8988529
  • 财政年份:
    2014
  • 资助金额:
    $ 1.92万
  • 项目类别:
活性化肝星細胞におけるinterferon-α,γ標的タンパク質の網羅的解析
活化肝星状细胞中干扰素α、γ靶蛋白的综合分析
  • 批准号:
    16790211
  • 财政年份:
    2004
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Anticancer therapy by hybrids of dendritic cells and interferon-α-overexpressing cells
树突状细胞和干扰素-α-过表达细胞的杂交抗癌治疗
  • 批准号:
    14570509
  • 财政年份:
    2002
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Recovery of Natural Interferon-α/β-producing Cells after Allogeneic Hematopoietic Stem Cell Transplantation
异体造血干细胞移植后天然干扰素-α/β产生细胞的恢复
  • 批准号:
    13671062
  • 财政年份:
    2001
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effect of Interferon-α treatment for HCV-positive renal transplant recipients and hempdialysed patients.
干扰素-α 治疗对 HCV 阳性肾移植受者和血液透析患者的影响。
  • 批准号:
    09671652
  • 财政年份:
    1997
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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